We propose to undertake the study of the immune lysis of blood cells particularly in malignant disease. We propose to continue our quantitative studies of the immunoglobulin and complement fixation in patients with autoimmune disease of the platelets and red cells in defining the role of antibody in cellular descruction. We will quantitate the IgG subclass constitution of these antibodies and the relationship of this to in vivo complement fixation and destructive rate. We will continue to develop the methodology for the quantitative detection of platelet antibodies in order to be able to cross-match platelets for transfusion. We will investigate immune cell-cell interaction by studying the quantitative relationships between the IgG subclass of antibody and the nature of the component of complement fixed to target cell in the interaction with effector cells of the immune system. Using these techniques, we will investigate the influence of alterations in the effector cell both induced in vitro and due to disease processes. In order to understand the genesis of antibody in autoimmune disease we will undertake to study the production of antibody to red cells by lymphocytes, both benign and malignant, particularly those responsible for the production of cold agglutinins. With this system, we will study the control of specific antibody production by cells and humoral factors. Finally, we will continue to study the relationship of membrane abnormalities to alterations in the susceptibility to the hemolytic action of complement, by searching for membrane proteins which might alter the rate or degree of C3 fixation to red cells.